Objective: To determine whether the incidence of clinically isolated syndrome (CIS) the precursor form of multiple sclerosis (MS) that encompasses optic neuritis and transverse myelitis as well as other clinical presentations, varies by race/ethnicity in a multi-ethnic, population-based cohort. Background We previously reported that the incidence of MS was higher in blacks than whites, Hispanics and Asians. Design/Methods: We used electronic record searches and complete medical records review to identify all newly diagnosed CIS and MS cases in the population-based, multiethnic membership of Southern California Kaiser Permanente (KPSC) between 2008 and 2009. The KPSC membership contributed 7,410,754 person-years of observation during the study period and the racial/ethnic distribution was 36.5% white, 8.6% black, 43.4% Hispanic, 9.3% Asian/Pacific Islanders (Asian/PI) and 1.9% other. Results: We identified 254 incident cases of CIS cases who did not yet met McDonald criteria for MS and did not have other obvious causes (e.g. viral, lupus, ischemia). The most common clinical presentation was optic neuritis (48.4%) followed by transverse myelitis (32.7%), other forms of mono-regional CIS (9.8%) and poly-regional CIS (9.1%). The average age at diagnosis with CIS was 42.9 years (range 14.8-80.8) and 70.5% were women. Among CIS cases, the racial/ethnic distribution was 47.6% white, 12.6% black, 33.1% Hispanic, 4.3% Asian/PI and 2.4% other. The incidence of CIS was 3.4 per 100,000 person-years. Incidence of CIS was higher in black (5.1, 95%CI=3.5-7.1) and white, non-Hispanic individuals (4.5, 95%CI=3.7-5.3) compared with white, Hispanic (2.6, 95%CI=2.1-3.2) and Asian/PI individuals (1.6, 95%CI=0.8-2.9; p Conclusions: The incidence of CIS is 3.4 per 100,000 person-years in a multi-ethnic, population-based cohort of Southern Californians. The incidence of CIS is higher in black and white individuals compared with Hispanic and Asian/PI individuals. Incidence rates standardized to the US census by age and gender will be presented at the meeting. Disclosure: Dr. Langer-Gould has nothing to disclose. Dr. Brara has nothing to disclose. Dr. Beaber has nothing to disclose. Dr. Zhang has nothing to disclose.